Project Goals and Objectives: Specific projects will 1) identify and characterize specific mechanisms used by pathogenic bacteria to evade or subvert normal phagocyte responses and therefore cause disease, and 2) investigate human phagocyte response mechanisms to pathogenic bacteria. Research Accomplishments: 1) We have determined that Group A Streptococcus secretes a homologue of human CD11b that blocks innate and acquired immune function. This represents a novel mechanism by which Group A Streptococcus can survive during the course of human infection. 2)We used human oligonucleotide microarrays (Affymetrix GeneChip) to determine global gene expression profiles in human PMNs during receptor-mediated phagocytosis. We discovered that gene transcription following phagocytosis serves mainly to determine PMN fate. We identified entire apoptotic pathways (>100 genes) for activated human PMNs and for those undergoing spontaneous apoptosis. These studies will be used as a springboard for studies with human pathogens.